CircRNA: a rising star in gastric cancer

  • Rong Li
  • Jiajia Jiang
  • Hui Shi
  • Hui Qian
  • Xu ZhangEmail author
  • Wenrong XuEmail author


In recent years, a large number of circRNAs have been identified in mammalian cells with high-throughput sequencing technologies and bioinformatics. The aberrant expression of circRNAs has been reported in many human diseases including gastric cancer (GC). The number of GC-related circRNAs with validated biological functions and mechanisms of action is growing. CircRNAs are critically involved in GC cell proliferation, apoptosis, migration, and invasion. CircRNAs have been shown to function as regulators of parental gene transcription and alternative splicing and miRNA sponges. Moreover, circRNAs have been suggested to interact with proteins to regulate their expression level and activities. Several circRNAs have been identified to encode functional proteins. Due to their great abundance, high stability, tissue- and developmental-stage-specific expression patterns, and wide distribution in various body fluids and exosomes, circRNAs exhibit a great potential to be utilized as biomarkers for GC. Herein, we briefly summarize their biogenesis, properties and biological functions and discuss about the current research progress of circRNAs in GC with a focus on the potential application for GC diagnosis and therapy.


CircRNA Gastric cancer miRNA sponge Biomarker Therapeutic target 



Gastric cancer


Exonic circRNAs


Intronic circRNAs


Exon–intron circular RNAs


TRNA intronic circRNAs








Epithelial-mesenchymal transition


RNA-binding proteins


TRNA splicing endonuclease complex




Hepatocellular carcinoma


Esophageal squamous cell carcinoma


Internal ribosome entry sites


Cyclin-dependent kinase 2




Pescadillo homologue 1


Argonauto 2


Area under the ROC curve


Exosomes-derived circRNAs


Cancer-associated fibroblasts


Small interfering RNAs



This work was supported by the National Natural Science Foundation of China (Grant 81572075, Grant 81972310), Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application (Grant SS2018003), and Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

Author contributions

RL and JJ collected literature and draft the manuscript. HS, XZ, HQ and WX reviewed and made significant revisions to the manuscript. All authors have read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


  1. 1.
    Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F (2014) Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomark 23(5):700–713CrossRefGoogle Scholar
  3. 3.
    Triantafillidis JK, Cheracakis P (2003) Gastric cancer: recent developments in its etiology and pathogenesis. Ann Gastroenterol 16(1):12–19Google Scholar
  4. 4.
    Zhang X, Zhang W, Yuan X, Fu M, Qian H, Xu W (2016) Neutrophils in cancer development and progression: roles, mechanisms, and implications (Review). Int J Oncol 49(3):857–867PubMedCrossRefGoogle Scholar
  5. 5.
    Wu L, Xu Z, Zhang B, Hui S, Xiao Y, Sun Y, Pan Z, Hui Q, Xu W (2016) Exosomes derived from gastric cancer cells activate NF-κB pathway in macrophages to promote cancer progression. Tumor Biol 37(9):12169–12180CrossRefGoogle Scholar
  6. 6.
    Xue Y, Jing H, Han Z, Ying W, Chong H, Wei L, Shi Y (2013) One cell, multiple roles: contribution of mesenchymal stem cells to tumor development in tumor microenvironment. Cell Biosci 3(1):5CrossRefGoogle Scholar
  7. 7.
    Ajani JA, Bentrem DJ, Besh S, D’Amico TA, Das P, Denlinger C, Fakih MG, Fuchs CS, Gerdes H, Glasgow RE (2013) Gastric cancer, version 2.2013: featured updates to the NCCN Guidelines. J Natl Compr Canc Netw 11(5):531–546PubMedCrossRefGoogle Scholar
  8. 8.
    Chiurillo MA (2015) Role of the Wnt/β-catenin pathway in gastric cancer: an in-depth literature review. World J Exp Med 5(2):84–102PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Sanger HL, Klotz G, Riesner D, Gross HJ, Kleinschmidt AK (1976) Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Proc Natl Acad Sci USA 73(11):3852–3856PubMedCrossRefGoogle Scholar
  10. 10.
    Salzman J, Gawad C, Wang PL, Lacayo N, Brown PO (2012) Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types. PLoS One 7(2):e30733PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Jeck WR, Sorrentino JA, Wang K, Slevin MK, Burd CE, Liu J, Marzluff WF, Sharpless NE (2013) Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA 19(2):141–157PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, Maier L, Mackowiak SD, Gregersen LH, Munschauer M, Loewer A, Ziebold U, Landthaler M, Kocks C, le Noble F, Rajewsky N (2013) Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495(7441):333–338PubMedCrossRefGoogle Scholar
  13. 13.
    Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, Kjems J (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495(7441):384–388PubMedCrossRefGoogle Scholar
  14. 14.
    Zhao Y, Alexandrov PN, Jaber V, Lukiw WJ (2016) Deficiency in the ubiquitin conjugating enzyme UBE2A in Alzheimer’s disease (AD) is linked to deficits in a natural circular miRNA-7 sponge (circRNA; ciRS-7). Genes 7(12):116PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Xu H, Guo S, Li W, Yu P (2015) The circular RNA Cdr1as, via miR-7 and its targets, regulates insulin transcription and secretion in islet cells. Sci Rep 5(1):12453PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Holdt LM, Stahringer A, Sass K, Pichler G, Kulak NA, Wilfert W, Kohlmaier A, Herbst A, Northoff BH, Nicolaou A (2016) Circular non-coding RNA ANRIL modulates ribosomal RNA maturation and atherosclerosis in humans. Nat Commun 7:12429PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Zhang M, Huang N, Yang X, Luo J, Yan S, Xiao F, Chen W, Gao X, Zhao K, Zhou H, Li Z, Ming L, Xie B, Zhang N (2018) A novel protein encoded by the circular form of the SHPRH gene suppresses glioma tumorigenesis. Oncogene 37(13):1805–1814PubMedCrossRefGoogle Scholar
  18. 18.
    Guarnerio J, Bezzi M, Jeong JC, Paffenholz SV, Berry K, Naldini MM, Lococo F, Tay Y, Beck AH, Pandolfi PP (2016) Oncogenic role of fusion-circRNAs derived from cancer-associated chromosomal translocations. Cell 165(2):289–302PubMedCrossRefGoogle Scholar
  19. 19.
    Zhang Y, Zhang XO, Chen T, Xiang JF, Yin QF, Xing YH, Zhu S, Yang L, Chen LL (2013) Circular intronic long noncoding RNAs. Mol Cell 51(6):792–806PubMedCrossRefGoogle Scholar
  20. 20.
    Li Z, Huang C, Bao C, Chen L, Lin M, Wang X, Zhong G, Yu B, Hu W, Dai L (2015) Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol 22(3):256–264PubMedCrossRefGoogle Scholar
  21. 21.
    Zhang XO, Wang HB, Zhang Y, Lu X, Chen LL, Yang L (2014) Complementary sequence-mediated exon circularization. Cell 159(1):134–147PubMedCrossRefGoogle Scholar
  22. 22.
    Liang D, Wilusz JE (2014) Short intronic repeat sequences facilitate circular RNA production. Genes Dev 28(20):2233–2247PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Zhipeng L, Filonov GS, Noto JJ, Schmidt CA, Hatkevich TL, Ying W, Jaffrey SR, Gregory AM (2015) Metazoan tRNA introns generate stable circular RNAs in vivo. RNA 21(9):1554–1565CrossRefGoogle Scholar
  24. 24.
    Ashwal-Fluss R, Meyer M, Pamudurti NR, Ivanov A, Bartok O, Hanan M, Evantal N, Memczak S, Rajewsky N, Kadener S (2014) CircRNA biogenesis competes with pre-mRNA splicing. Mol Cell 56(1):55–66PubMedCrossRefGoogle Scholar
  25. 25.
    Ivanov A, Memczak S, Wyler E, Torti F, Porath HT, Orejuela MR, Piechotta M, Levanon EY, Landthaler M, Dieterich C, Rajewsky N (2015) Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals. Cell Rep 10(2):170–177PubMedCrossRefGoogle Scholar
  26. 26.
    Conn S, Pillman K, Toubia J, Conn V, Salmanidis M, Phillips C, Roslan S, Schreiber A, Gregory P, Goodall G (2015) The RNA binding protein Quaking regulates formation of circRNAs. Cell 160(6):1125–1134PubMedCrossRefGoogle Scholar
  27. 27.
    Lasda E, Parker R (2014) Circular RNAs: diversity of form and function. RNA 20(12):1829–1842. CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Danan M, Schwartz S, Edelheit S, Sorek R (2012) Transcriptome-wide discovery of circular RNAs in Archaea. Nucleic Acids Res 40(7):3131–3142PubMedCrossRefGoogle Scholar
  29. 29.
    Ye CY, Chen L, Liu C, Zhu QH, Fan L (2015) Widespread noncoding circular RNAs in plants. New Phytol 208(1):88–95PubMedCrossRefGoogle Scholar
  30. 30.
    Huang C, Liang D, Tatomer DC, Wilusz JE (2018) A length-dependent evolutionarily conserved pathway controls nuclear export of circular RNAs. Genes Dev 32(9–10):639–644PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Wang PL, Bao Y, Yee MC, Barrett SP, Hogan GJ, Olsen MN, Dinneny JR, Brown PO, Salzman J (2014) Circular RNA is expressed across the eukaryotic tree of life. PLoS One 9(6):e90859PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Thomas LF (2014) Circular RNAs are depleted of polymorphisms at microRNA binding sites. Bioinformatics 30(16):2243–2246PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Suzuki H, Tsukahara T (2014) A view of pre-mRNA splicing from RNase R resistant RNAs. Int J Mol Sci 15(6):9331–9342PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Vicens Quentin, Westhof Eric (2014) Biogenesis of circular RNAs. Cell 159(1):13–14PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Jeck WR, Sharpless NE (2014) Detecting and characterizing circular RNAs. Nat Biotechnol 32(5):453–461PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Hansen TB, Wiklund ED, Bramsen JB, Villadsen SB, Statham AL, Clark SJ, Kjems J (2011) MiRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA. EMBO J 30(21):4414–4422PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Salzman J, Chen RE, Olsen MN, Wang PL, Brown PO (2013) Cell-type specific features of circular RNA expression. PLoS Genet 9(9):e1003777PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Venø MT, Hansen TB, Venø ST, Clausen BH, Grebing M, Finsen B, Holm IE, Kjems J (2015) Spatio-temporal regulation of circular RNA expression during porcine embryonic brain development. Genome Biol 16(1):245PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Szabo L, Morey R, Palpant NJ, Wang PL, Afari N, Jiang C, Parast MM, Murry CE, Laurent LC, Salzman J (2015) Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development. Genome Biol 16(1):126PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Ambros V (2004) The functions of animal microRNAs. Nature 431(7006):350–355PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Geng HH, Rui L, Su YM, Jie X, Min P, Cai XX, Ji XP (2016) The circular RNA Cdr1as promotes myocardial infarction by mediating the regulation of miR-7a on its target genes expression. PLoS One 11(3):e0151753PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Yu L, Gong X, Sun L, Zhou Q, Lu B, Zhu L (2016) The circular RNA Cdr1as act as an oncogene in hepatocellular carcinoma through targeting miR-7 expression. PLoS One 11(7):e0158347PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Pan H, Li T, Jiang Y, Pan C, Ding Y, Huang Z, Yu H, Kong D (2018) Overexpression of circular RNA ciRS-7 abrogates the tumor suppressive effect of miR-7 on gastric cancer via PTEN/PI3K/AKT signaling pathway. J Cell Biochem 119(1):440–446PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Xie H, Ren X, Xin S, Lan X, Lu G, Yuan L, Yang S, Zeng Z, Liao W, Ding YQ (2016) Emerging roles of circRNA_001569 targeting miR-145 in the proliferation and invasion of colorectal cancer. Oncotarget 7(18):26680–26691PubMedPubMedCentralGoogle Scholar
  45. 45.
    Han D, Li J, Wang H, Su X, Hou J, Gu Y, Qian C, Lin Y, Liu X, Huang M (2017) Circular RNA MTO1 acts as the sponge of miR-9 to suppress hepatocellular carcinoma progression. Hepatology 66(4):1151–1164PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Zhong Z, Lv M, Chen J (2016) Screening differential circular RNA expression profiles reveals the regulatory role of circTCF25-miR-103a-3p/miR-107-CDK6 pathway in bladder carcinoma. Sci Rep 6:30919PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Ebbesen KK, Kjems J, Hansen TB (2016) Circular RNAs: identification, biogenesis and function. Biochim Biophys Acta 1859 1:163–168Google Scholar
  48. 48.
    Chao CW, Chan DC, Kuo A, Leder P (1998) The mouse formin (Fmn) gene: abundant circular RNA transcripts and gene-targeted deletion analysis. Mol Med 4(9):614–628PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Gualandi F, Trabanelli C, Rimessi P, Calzolari E, Toffolatti L, Patarnello T, Kunz G, Muntoni F, Ferlini A (2003) Multiple exon skipping and RNA circularisation contribute to the severe phenotypic expression of exon 5 dystrophin deletion. J Med Genet 40(8):e100PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Wang Y, Wang Z (2015) Efficient backsplicing produces translatable circular mRNAs. RNA 21(2):172–179PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Chen CY, Sarnow P (1995) Initiation of protein synthesis by the eukaryotic translational apparatus on circular RNAs. Science 268(5209):415–417PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Yang Y, Fan X, Mao M, Song X, Wu P, Zhang Y, Jin Y, Yang Y, Chen L, Wang Y (2017) Extensive translation of circular RNAs driven by N6-methyladenosine. Cell Res 27(5):626–641PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Pamudurti NR, Bartok O, Jens M, Ashwalfluss R, Stottmeister C, Ruhe L, Hanan M, Wyler E, Perezhernandez D, Ramberger E (2017) Translation of circRNAs. Mol Cell 66(1):9–21PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Zhang M, Huang N, Yang X, Luo J, Yan S, Xiao F, Chen W, Gao X, Zhao K, Zhou H (2018) A novel protein encoded by the circular form of the SHPRH gene suppresses glioma tumorigenesis. Oncogene 37(13):1805–1814PubMedCrossRefGoogle Scholar
  55. 55.
    Granados-Riveron JT, Aquino-Jarquin G (2016) The complexity of the translation ability of circRNAs. Biochim Biophys Acta 1859 10:1245–1251Google Scholar
  56. 56.
    Du WW, Yang W, Chen Y, Wu ZK, Foster FS, Yang Z, Li X, Yang BB (2016) Foxo3 circular RNA promotes cardiac senescence by modulating multiple factors associated with stress and senescence responses. Eur Heart J 38(18):1402–1412Google Scholar
  57. 57.
    Xia P, Wang S, Ye B, Du Y, Li C, Xiong Z, Qu Y, Fan Z (2018) A circular RNA protects dormant hematopoietic stem cells from DNA sensor cGAS-mediated exhaustion. Immunity 48(4):688–701PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Abdelmohsen K, Panda AC, Munk R, Grammatikakis I, Dudekula DB, De S, Kim J, Noh JH, Kim KM, Martindale JL (2017) Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1. RNA Biol 14(3):361–369PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Yang Q, Du WW, Wu N, Yang W, Awan FM, Fang L, Ma J, Li X, Zeng Y, Yang Z, Dong J, Khorshidi A, Yang BB (2017) A circular RNA promotes tumorigenesis by inducing c-myc nuclear translocation. Cell Death Differ 24(9):1609–1620PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Ghosal S, Das S, Sen R, Basak P, Chakrabarti J (2013) Circ2Traits: a comprehensive database for circular RNA potentially associated with disease and traits. Front Genet 4:283PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Li JH, Liu S, Zhou H, Qu LH, Yang JH (2014) StarBase v20: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res 42:92–97 (Database issue) CrossRefGoogle Scholar
  62. 62.
    Dudekula DB, Panda AC, Grammatikakis I, De S, Abdelmohsen K, Gorospe M (2016) CircInteractome: a web tool for exploring circular RNAs and their interacting proteins and microRNAs. RNA Biol 13(1):34–42PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Chen X, Ping H, Tao Z, Guo X, Song X, Yan L (2016) CircRNADb: a comprehensive database for human circular RNAs with protein-coding annotations. Sci Rep 6:34985PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Xia S, Feng J, Chen K, Ma Y, Gong J, Cai F, Jin Y, Gao Y, Xia L, Chang H (2018) CSCD: a database for cancer-specific circular RNAs. Nucleic Acids Res 46(D1):D925–D929PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    Tang Z, Li X, Zhao J, Qian F, Feng C, Li Y, Zhang J, Jiang Y, Yang Y, Wang Q, Li C (2018) TRCirc: a resource for transcriptional regulation information of circRNAs. Brief Bioinform. CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Glažar P, Papavasileiou P, Rajewsky N (2014) CircBase: a database for circular RNAs. RNA 20(11):1666–1670PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Liu YC, Li JR, Sun CH, Erik A, Chao RF, Lin FM, Weng SL, Sheng-Da H, Huang CC, Chao C (2016) CircNet: a database of circular RNAs derived from transcriptome sequencing data. Nucleic Acids Res 44(D1):D209–D215PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Zheng LL, Li JH, Jie W, Sun WJ, Liu S, Wang ZL, Hui Z, Yang JH, Qu LH (2016) DeepBase v2.0: identification, expression, evolution and function of small RNAs, LncRNAs and circular RNAs from deep-sequencing data. Nucleic Acids Res 44(D1):D196–202PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Zhao Z, Wang K, Wu F, Wang W, Zhang K, Hu H, Liu Y, Jiang T (2018) CircRNA disease: a manually curated database of experimentally supported circRNA-disease associations. Cell Death Dis 9(5):475PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Dong R, Ma XK, Li GW, Yang L (2018) CIRCpedia v2: an updated database for comprehensive circular RNA annotation and expression comparison. Genomics Proteomics Bioinform 16(4):226–233CrossRefGoogle Scholar
  71. 71.
    Sui W, Shi Z, Xue W, Ou M, Zhu Y, Chen J, Lin H, Liu F, Dai Y (2017) Circular RNA and gene expression profiles in gastric cancer based on microarray chip technology. Oncol Rep 37(3):1804–1814PubMedCrossRefGoogle Scholar
  72. 72.
    Huang YS, Jie N, Zou KJ, Weng Y (2017) Expression profile of circular RNAs in human gastric cancer tissues. Mol Med Rep 16(3):2469–2476PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Fang Y, Ma M, Wang J, Liu X, Wang Y (2017) Circular RNAs play an important role in late-stage gastric cancer: circular RNA expression profiles and bioinformatics analyses. Tumour Biol 39(6):1010428317705850PubMedCrossRefGoogle Scholar
  74. 74.
    Shao Y, Li J, Lu R, Li T, Yang Y, Xiao B, Guo J (2017) Global circular RNA expression profile of human gastric cancer and its clinical significance. Cancer Med 6(6):1173–1180PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Chen J, Li Y, Zheng Q, Bao C, He J, Chen B, Lyu D, Zheng B, Xu Y, Long Z, Zhou Y, Zhu H, Wang Y, He X, Shi Y, Huang S (2017) Circular RNA profile identifies circPVT1 as a proliferative factor and prognostic marker in gastric cancer. Cancer Lett 388:208–219PubMedCrossRefGoogle Scholar
  76. 76.
    Vidal AF, Ribeirodossantos AM, Vinascosandoval T, Magalhães L, Pinto P, Anaissi AKM, Demachki S, Assumpção PPD, Santos SEBD, RibeirodosSantos  (2017) The comprehensive expression analysis of circular RNAs in gastric cancer and its association with field cancerization. Sci Rep 7(1):14551PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Dang Y, Ouyang X, Zhang F, Wang K, Lin Y, Sun B, Wang Y, Wang L, Huang Q (2017) Circular RNAs expression profiles in human gastric cancer. Sci Rep 7(1):9060PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Li T, Shao Y, Fu L, Yi X, Zhu L, Sun W, Rui Y, Xiao B, Guo J (2018) Plasma circular RNA profiling of patients with gastric cancer and their droplet digital RT-PCR detection. J Mol Med 96(1):85–96PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Gu W, Sun Y, Zheng X, Ma J, Hu XY, Gao T, Hu MJ (2018) Identification of gastric cancer-related circular RNA through microarray analysis and bioinformatics analysis. Biomed Res Int. CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Pan H, Li T, Jiang Y, Pan C, Ding Y, Huang Z, Yu H, Kong D (2017) Overexpression of circular RNA ciRS-7 abrogates the tumor suppressive effect of miR-7 on Gastric cancer via PTEN/PI3 K/AKT signaling pathway. J Cell Biochem 119(1):440–446PubMedCrossRefGoogle Scholar
  81. 81.
    Pérezramírez C, Cañadasgarre M, Molina MÁ, Fausdáder MJ, Callejahernández MÁ (2015) PTEN and PI3 K/AKT in non-small-cell lung cancer. Pharmacogenomics 16(16):1843–1862CrossRefGoogle Scholar
  82. 82.
    Wang F, Li L, Chen Z, Zhu M, Gu Y (2016) MicroRNA-214 acts as a potential oncogene in breast cancer by targeting the PTEN-PI3K/Akt signaling pathway. Int J Mol Med 37(5):1421–1428PubMedCrossRefGoogle Scholar
  83. 83.
    Zheng L, Zhang Y, Liu Y, Zhou M, Lu Y, Yuan L, Zhang C, Hong M, Wang S, Li X (2015) MiR-106b induces cell radioresistance via the PTEN/PI3K/AKT pathways and p21 in colorectal cancer. J Transl Med 13:252PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Cheng J, Zhuo H, Xu M, Wang L, Xu H, Peng J, Hou J, Lin L, Cai J (2018) Regulatory network of circRNA–miRNA–mRNA contributes to the histological classification and disease progression in gastric cancer. J Transl Med 16(1):216PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Shen F, Liu P, Li N, Yi Z, Tie X, Zhang Y, Gao L, Xu Z (2018) CircRNA_001569 promotes cell proliferation through absorbing miR-145 in gastric cancer. J Biochem 165(1):27–36CrossRefGoogle Scholar
  86. 86.
    Xie H, Ren X, Xin S, Lan X, Lu G, Lin Y, Yang S, Zeng Z, Liao W, Ding YQ (2016) Emerging roles of circRNA_001569 targeting miR-145 in the proliferation and invasion of colorectal cancer. Oncotarget 7(18):26680–26691PubMedPubMedCentralGoogle Scholar
  87. 87.
    Ouyang Y, Li Y, Huang Y, Li X, Zhu Y, Long Y, Wang Y, Guo X, Gong K (2019) CircRNA circPDSS1 promotes the gastric cancer progression by sponging miR-186-5p and modulating NEK2. J Cell Physiol 234(7):10458–10469PubMedCrossRefGoogle Scholar
  88. 88.
    Hayward DG, Fry AM (2006) Nek2 kinase in chromosome instability and cancer. Cancer Lett 237(2):155–166PubMedCrossRefGoogle Scholar
  89. 89.
    Sun H, Xi P, Sun Z, Wang Q, Zhu B, Zhou J, Jin H, Zheng W, Tang W, Cao H, Cao X (2018) Circ-SFMBT2 promotes the proliferation of gastric cancer cells through sponging miR-182-5p to enhance CREB1 expression. Cancer Manag Res 10:5725–5734PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Wang Z, Ma K, Pitts S, Cheng Y, Liu X, Ke X, Kovaka S, Ashktorab H, Smoot DT, Schatz M, Wang Z, Meltzer S (2018) Novel circular RNA NF1 acts as a molecular sponge, promoting gastric cancer by absorbing miR-16. Endocr Relat Cancer 26(3):265–277Google Scholar
  91. 91.
    Zhang Y, Liu H, Li W, Yu J, Li J, Shen Z, Ye G, Qi X, Li G (2017) CircRNA_100269 is downregulated in gastric cancer and suppresses tumor cell growth by targeting miR-630. Aging (Albany NY) 9(6):1585–1594CrossRefGoogle Scholar
  92. 92.
    Zhang S, Zhang JY, Lu LJ, Wang CH, Wang LH (2017) MiR-630 promotes epithelial ovarian cancer proliferation and invasion via targeting KLF6. Eur Rev Med Pharmacol Sci 21(20):4542–4547PubMedGoogle Scholar
  93. 93.
    Li J, Zhen L, Zhang Y, Zhao L, Liu H, Cai D, Chen H, Yu J, Qi X, Li G (2017) Circ-104916 is downregulated in gastric cancer and suppresses migration and invasion of gastric cancer cells. Onco Targets Ther 10:3521–3529PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Zhao JJ, Chen PJ, Duan RQ, Li KJ, Wang YZ, Li Y (2016) miR-630 functions as a tumor oncogene in renal cell carcinoma. Arch of Med Sci 12(3):473–478CrossRefGoogle Scholar
  95. 95.
    Zhang JW, Li Y, Zeng XC, Zhang T, Fu BS, Yi HM, Zhang Q, Jiang N (2015) MiR-630 overexpression in hepatocellular carcinoma tissues is positively correlated with alpha-fetoprotein. Med Sci Monit 21:667–673PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Liu H, Liu Y, Bian Z, Zhang J, Zhang R, Chen X, Huang Y, Wang Y, Zhu J (2018) Circular RNA YAP1 inhibits the proliferation and invasion of gastric cancer cells by regulating the miR-367-5p/p27 Kip1 axis. Mol Cancer 17(1):151PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Kang W, Tong JH, Lung RW, Dong Y, Zhao J, Liang Q, Zhang L, Pan Y, Yang W, Pang JC (2015) Targeting of YAP1 by microRNA-15a and microRNA-16-1 exerts tumor suppressor function in gastric adenocarcinoma. Mol Cancer 14(1):52PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Zhang J, Liu H, Hou L, Wang G, Zhang R, Huang Y, Chen X, Zhu J (2017) Circular RNA_LARP4 inhibits cell proliferation and invasion of gastric cancer by sponging miR-424-5p and regulating LATS1 expression. Mol Cancer 16(1):151PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Yimlamai D, Fowl BH, Camargo FD (2015) Emerging evidence on the role of the Hippo/YAP pathway in liver physiology and cancer. J Hepatol 63(6):1491–1501PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Zhou GX, Li XY, Zhang Q, Zhao K, Zhang CP, Xue CH, Yang K, Tian ZB (2013) Effects of the hippo signaling pathway in human gastric cancer. Asian Pac J Cancer Prev 14(9):5199–5205PubMedCrossRefGoogle Scholar
  101. 101.
    Liu T, Liu S, Xu Y, Shu R, Wang F, Chen C, Zeng Y, Luo H (2018) Circular RNA-ZFR inhibited cell proliferation and promoted apoptosis in gastric cancer by sponging miR-130a/miR-107 and modulating PTEN. Cancer Res Treat 50(4):1396–1417PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Fang J, Hong H, Xue X, Zhu X, Jiang L, Qin M, Liang H, Gao L (2019) A novel circular RNA, circFAT1(e2), inhibits gastric cancer progression by targeting miR-548 g in the cytoplasm and interacting with YBX1 in the nucleus. Cancer Lett 442:222–232PubMedCrossRefGoogle Scholar
  103. 103.
    Prabhu L, Hartley A-V, Martin M, Warsame F, Sun E, Lu T (2015) Role of post-translational modification of the Y box binding protein 1 in human cancers. Genes Dis 2(3):240–246PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Wang L, Shen J, Jiang Y (2018) Circ_0027599/PHDLA1 suppresses gastric cancer progression by sponging miR-101-3p.1. Cell Biosci 8(1):58PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Li P, Chen H, Chen S, Mo X, Li T, Xiao B, Rui Y, Guo J (2017) Circular RNA 0000096 affects cell growth and migration in gastric cancer. Br J Cancer 116(5):626–633PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Zhou LH, Yang YC, Zhang RY, Wang P, Pang MH, Liang LQ (2018) CircRNA_0023642 promotes migration and invasion of gastric cancer cells by regulating EMT. Eur Rev Med Pharmacol Sci 22(8):2297–2303PubMedGoogle Scholar
  107. 107.
    Sun HD, Xu ZP, Sun ZQ, Zhu B, Wang Q, Zhou J, Jin H, Zhao A, Tang WW, Cao XF (2018) Down-regulation of circPVRL3 promotes the proliferation and migration of gastric cancer cells. Sci Rep 8(1):10111PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Lai Z, Yang Y, Yan Y, Li T, Li YS, Wang Z, Shen Z, Ye YJ, Jiang KW, Wang S (2017) Analysis of co-expression networks for circular RNAs and mRNAs reveals that circular RNAs hsa_circ_0047905, hsa_circ_0138960 and has-circRNA7690-15 are candidate oncogenes in gastric cancer. Cell Cycle 16(23):2301–2311PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Memczak S, Papavasileiou P, Peters O, Rajewsky N (2015) Identification and characterization of circular RNAs as a new class of putative biomarkers in human blood. PLoS One 10(10):e0141214PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Lin X, Lo HC, Wong DTW, Xiao X (2015) Noncoding RNAs in human saliva as potential disease biomarkers. Front Genet 6:175PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Li Y, Zheng Q, Bao C, Li S, Guo W, Zhao J, Chen D, Gu J, He X, Huang S (2015) Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Cell Res 25(8):981–984PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Sun H, Tang W, Rong D, Jin H, Fu K, Zhang W, Liu Z, Cao H, Cao X (2018) Hsa_circ_0000520, a potential new circular RNA biomarker, is involved in gastric carcinoma. Cancer Biomark 21(2):299–306PubMedCrossRefGoogle Scholar
  113. 113.
    Chen S, Li T, Zhao Q, Xiao B, Guo J (2017) Using circular RNA hsa_circ_0000190 as a new biomarker in the diagnosis of gastric cancer. Clin Chim Acta 466:167–171PubMedCrossRefGoogle Scholar
  114. 114.
    Huang M, He YR, Liang LC, Huang Q, Zhu ZQ (2017) Circular RNA hsa_circ_0000745 may serve as a diagnostic marker for gastric cancer. World J Gastroenterol 23(34):6330–6338PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Lasda E, Parker R (2016) Circular RNAs co-precipitate with extracellular vesicles: a possible mechanism for circRNA clearance. PLoS One 11(2):e0148407PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Piwecka M, Glažar P, Hernandez-Miranda LR, Memczak S, Wolf SA, Rybak-Wolf A, Filipchyk A, Klironomos F, Cerda Jara CA, Fenske P (2017) Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function. Science. CrossRefPubMedGoogle Scholar
  117. 117.
    Yao Z, Luo J, Hu K, Lin J, Huang H, Wang Q, Zhang P, Xiong Z, He C, Huang Z (2017) ZKSCAN1 gene and its related circular RNA (circZKSCAN1) both inhibit hepatocellular carcinoma cell growth, migration, and invasion but through different signaling pathways. Mol Oncol 11(4):422–437PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Liu X, Abraham JM, Cheng Y, Wang Z, Wang Z, Zhang G, Ashktorab H, Smoot DT, Cole RN, Boronina TN, DeVine LR, Talbot CC Jr, Liu Z, Meltzer SJ (2018) Synthetic circular RNA functions as a miR-21 sponge to suppress gastric carcinoma cell proliferation. Mol Ther Nucleic Acids 13:312–321PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Qin J, Xu Q (2014) Functions and applications of exosomes. Acta Pol Pharm 71(4):537–543PubMedGoogle Scholar
  120. 120.
    Kumar L, Verma S, Vaidya B, Gupta V (2015) Exosomes: natural carriers for siRNA delivery. Curr Pharm Des 21(31):4556–4565PubMedCrossRefGoogle Scholar
  121. 121.
    Tian M, Chen R, Li T, Xiao B (2018) Reduced expression of circRNA hsa_circ_0003159 in gastric cancer and its clinical significance. J Clin Lab Anal 32(3):e22281CrossRefGoogle Scholar
  122. 122.
    Xie Y, Shao Y, Sun W, Ye G, Zhang X, Xiao B, Guo J (2018) Downregulated expression of hsa_circ_0074362 in gastric cancer and its potential diagnostic values. Biomark Med 12(1):11–20PubMedCrossRefGoogle Scholar
  123. 123.
    Shao Y, Chen L, Lu R, Zhang X, Xiao B, Ye G, Guo J (2017) Decreased expression of hsa_circ_0001895 in human gastric cancer and its clinical significances. Tumour Biol 39(4):1010428317699125PubMedCrossRefGoogle Scholar
  124. 124.
    Shao Y, Yang Y, Lu R, Xiao B, Ye G, Guo J (2017) Identification of tissue-specific circRNA hsa_circ_0000705 as an indicator for human gastric cancer. Int J Clin Exp Pathol 10(3):3151–3156Google Scholar
  125. 125.
    Lu R, Shao Y, Ye G, Xiao B, Guo J (2017) Low expression of hsa_circ_0006633 in human gastric cancer and its clinical significances. Tumour Biol 39(6):1010428317704175PubMedCrossRefGoogle Scholar
  126. 126.
    Li P, Chen S, Chen H, Mo X, Li T, Shao Y, Xiao B, Guo J (2015) Using circular RNA as a novel type of biomarker in the screening of gastric cancer. Clin Chim Acta 444:132–136PubMedCrossRefGoogle Scholar
  127. 127.
    Li WH, Song YC, Zhang H, Zhou ZJ, Xie X, Zeng QN, Guo K, Wang T, Xia P, Chang DM (2017) Decreased expression of hsa_circ_00001649 in gastric cancer and its clinical significance. Dis Markers 2017:4587698PubMedPubMedCentralGoogle Scholar
  128. 128.
    Tang W, Fu K, Sun H, Rong D, Wang H, Cao H (2018) CircRNA microarray profiling identifies a novel circulating biomarker for detection of gastric cancer. Mol Cancer 17(1):137PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Zhao Q, Chen S, Li T, Xiao B, Zhang X (2018) Clinical values of circular RNA 0000181 in the screening of gastric cancer. J Clin Lab Anal 32(4):e22333PubMedCrossRefGoogle Scholar
  130. 130.
    Lee K, Hwang H, Nam KT (2014) Immune response and the tumor microenvironment: how they communicate to regulate gastric cancer. Gut Liver 8(2):131–139PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Wu X, Tao P, Zhou Q, Li J, Yu Z, Wang X, Li J, Li C, Yan M, Zhu Z, Liu B, Su L (2017) IL-6 secreted by cancer-associated fibroblasts promotes epithelial-mesenchymal transition and metastasis of gastric cancer via JAK2/STAT3 signaling pathway. Oncotarget 8(13):20741–20750PubMedPubMedCentralGoogle Scholar
  132. 132.
    Zhang H, Zhu L, Bai M, Liu Y, Zhan Y, Deng T, Yang H, Sun W, Wang X, Zhu K, Fan Q, Li J, Ying G, Ba Y (2019) Exosomal circRNA derived from gastric tumor promotes white adipose browning by targeting the miR-133/PRDM16 pathway. Int J Cancer 144(10):2501–2515PubMedCrossRefPubMedCentralGoogle Scholar
  133. 133.
    Bär C, Thum T, Gonzalo-Calvo D (2019) Circulating miRNAs as mediators in cell-to-cell communication. Epigenomics 11(2):111–113PubMedCrossRefGoogle Scholar
  134. 134.
    Kim KM, Abdelmohsen K, Mustapic M, Kapogiannis D, Gorospe M (2017) RNA in extracellular vesicles. Wiley Interdiscip Rev RNA 8(4):e1413CrossRefGoogle Scholar
  135. 135.
    Li Z, Yanfang W, Li J, Jiang P, Peng T, Chen K, Zhao X, Zhang Y, Zhen P, Zhu J, Li X (2018) Tumor-released exosomal circular RNA PDE8A promotes invasive growth via the miR-338/MACC1/MET pathway in pancreatic cancer. Cancer Lett 432:237–250PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Aoyang Institute of CancerJiangsu UniversitySuzhouChina
  2. 2.Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of MedicineJiangsu UniversityZhenjiangChina

Personalised recommendations